Dataset Information

Sequence features associated with microRNA strand selection in humans and flies.

ABSTRACT: BACKGROUND:During microRNA (miRNA) maturation in humans and flies, Drosha and Dicer cut the precursor transcript, thereby producing a short RNA duplex. One strand of this duplex becomes a functional component of the RNA-Induced Silencing Complex (RISC), while the other is eliminated. While thermodynamic asymmetry of the duplex ends appears to play a decisive role in the strand selection process, the details of the selection mechanism are not yet understood. RESULTS:Here, we assess miRNA strand selection bias in humans and fruit flies by analyzing the sequence composition and relative expression levels of the two strands of the precursor duplex in these species. We find that the sequence elements associated with preferential miRNA strand selection and/or rejection differ between the two species. Further, we identify another feature that distinguishes human and fly miRNA processing machinery: the relative accuracy of the Drosha and Dicer enzymes. CONCLUSION:Our result provides clues to the mechanistic aspects of miRNA strand selection in humans and other mammals. Further, it indicates that human and fly miRNA processing pathways are more distinct than currently recognized. Finally, the observed strand selection determinants are instrumental in the rational design of efficient miRNA-based expression regulators.

SUBMITTER: Hu HY

PROVIDER: S-EPMC2751786 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature

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Sequence features associated with microRNA strand selection in humans and flies.

Hu Hai Yang HY Yan Zheng Z Xu Ying Y Hu Hao H Menzel Corinna C Zhou Yan Hong YH Chen Wei W Khaitovich Philipp P

BMC genomics 20090904

<h4>Background</h4>During microRNA (miRNA) maturation in humans and flies, Drosha and Dicer cut the precursor transcript, thereby producing a short RNA duplex. One strand of this duplex becomes a functional component of the RNA-Induced Silencing Complex (RISC), while the other is eliminated. While thermodynamic asymmetry of the duplex ends appears to play a decisive role in the strand selection process, the details of the selection mechanism are not yet understood.<h4>Results</h4>Here, we assess ...[more]

PMID: 19732433

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Project description:MotivationMicroRNAs (miRNAs) play important roles in general biological processes and diseases pathogenesis. Identifying miRNA target genes is an essential step to fully understand the regulatory effects of miRNAs. Many computational methods based on the sequence complementary rules and the miRNA and mRNA expression profiles have been developed for this purpose. It is noted that there have been many sequence features of miRNA targets available, including the context features of the target sites, the thermodynamic stability and the accessibility energy for miRNA-mRNA interaction. However, most of current computational methods that combine sequence and expression information do not effectively integrate full spectrum of these features; instead, they perceive putative miRNA-mRNA interactions from sequence-based prediction as equally meaningful. Therefore, these sequence features have not been fully utilized for improving miRNA target prediction.ResultsWe propose a novel regularized regression approach that is based on the adaptive Lasso procedure for detecting functional miRNA-mRNA interactions. Our method fully takes into account the gene sequence features and the miRNA and mRNA expression profiles. Given a set of sequence features for each putative miRNA-mRNA interaction and their expression values, our model quantifies the down-regulation effect of each miRNA on its targets while simultaneously estimating the contribution of each sequence feature to predicting functional miRNA-mRNA interactions. By applying our model to the expression datasets from two cancer studies, we have demonstrated our prediction results have achieved better sensitivity and specificity and are more biologically meaningful compared with those based on other methods.Availability and implementationThe source code is available at: http://nba.uth.tmc.edu/homepage/liu/miRNALasso.Supplementary informationSupplementary data are available at Bioinformatics online.ContactYin.Liu@uth.tmc.edu.

Dataset Information

Sequence features associated with microRNA strand selection in humans and flies.

Publications

Sequence features associated with microRNA strand selection in humans and flies.

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